Testing of chemicals

Adverse Outcome Pathways, Molecular Screening and Toxicogenomics



20/09/2016 - OECD launched a new Series on Adverse Outcome Pathways on i-Library

OECD launched its knowledge base on Adverse Outcome Pathways (AOPs) in collaboration with the U.S Environmental Protection Agency and the European Commission Joint Research Centre in 2014. Two years later, the first five endorsed AOPs have been published in a new OECD Series on Adverse Outcome Pathways, available free of charge on the OECD public website. These publications are the result of joint efforts between AOP developers and AOP reviewers through an established OECD AOP development and review process. The first publication in the Series proposes a user guide for developing AOPs.

  1. Adverse Outcome Pathway on Protein Alkylation Leading to Liver Fibrosis
  2. Adverse Outcome Pathway on Alkylation of DNA in Male Pre-Meiotic Germ Cells Leading to Heritable Mutations
  3. Adverse Outcome Pathway on Aromatase Inhibition Leading to Reproductive Dysfunction (in Fish)
  4. Adverse Outcome Pathway on chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
  5. Adverse Outcome Pathway on binding of agonists to ionotropic glutamate receptors in adult brain leading to excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment

In the future, the publication of AOPs is likely to happen on a yearly basis, following the cycle of annual reviews and publications.

An AOP on the AOP Wiki is essentially a living document and may be regularly updated, since AOP development is based on crowdsourcing using the collaborative Wiki platform. An AOP published in the new OECD Series corresponds to an advanced snapshot-version of the AOP that has been thoroughly discussed and reviewed by the scientific community in accordance with OECD procedures.



The OECD launched a new programme on the development of Adverse Outcome Pathways (AOP) in 2012. An AOP is an analytical construct that describes a sequential chain of causally linked events at different levels of biological organisation that lead to an adverse health or ecotoxicological effect (see Figure). AOPs are the central element of a toxicological knowledge framework being built to support chemical risk assessment based on mechanistic reasoning.

Figure: Schematic representation of the Adverse Outcome Pathway illustrated with reference to a number of pathways

AOP image

‌‌‌The AOP development programme addresses the needs of:

  • the OECD Test Guidelines Programme for the identification of new biomarker endpoints and  in vitro test methods that are candidates to become part of OECD Test Guidelines

  • the OECD QSAR Project for the identification of new methods/profilers for grouping chemicals, and

This video explains the OECD work on Adverse Outcome Pathways and scientific developents in this area.

The OECD co-ordinates its activities with the WHO/IPCS work on Mode of Action, as the AOP concept and the Mode of Action are closely related.


 Useful links



Guidance, template, format available
AOP project proposal form

Note: With experience gained from the AOP developers and the development of the Users' handbook, parts of the Guidance Document below have become obsolete. An updated version will be available in 2016.

Guidance document and template for developing and assessing adverse outcome pathways

(Series No. 184, Series on Testing and Assessment)

User Handbook (No1 in OECD Series on Adverse Outcome Pathways)

AOP for skin sensitisation: Part 1 - Scientific Evidence

AOP for skin sensitisation: Part 2 - Use of the AOP to Develop Chemical Categories and Integrated Assessment and Testing Approaches

(Series No. 168, Series on Testing and Assessment)


How to make a project proposal

Project proposals for developing an AOP can be sent to the OECD Secretariat using the submission of proposals form (word file). Government representatives, academic experts, industry experts, non-governmental organisations, scientific societies, etc. can submit project proposals. The National Coordinators of the Test Guidelines Programme are available for queries, and should be informed about proposals submitted.

Project proposals are reviewed twice a year and included in the AOP workplan if justified. Browse the list of projects already in the workplan.


Process for the development and review of AOPs at OECD

The AOP development and review process is illustrated below. 

 The AOP development Programme is overseen by the Extended Advisory Group on Molecular Screening and Toxicogenomics (EAGMST)

The AOP review process

The AOP development Programme is overseen by the Extended Advisory Group on Molecular Screening and Toxicogenomics (EAGMST). EAGMST members are nominated by their National Coordinators; they play an active role in the development of AOPs, as well as in the internal review and approval process.

The review process is split in two phases, an internal review and an external review, followed by endorsement by the Working of the National Coordinators of the Test Guidelines Programme (WNT) and by the Task Force on Hazard Assessment (TFHA), and ultimately, the publication of AOPs in the OECD Series on AOPs. The publication in the OECD Series does not preclude the publication by authors of the AOP in the scientific literature. The main objective of the internal review (conducted within the EAGMST, by EAGMST members) is to check compliance of the AOP structure and content with the User's Handbook and guidance principles, while the objective of the external review is to assess the scientific/technical content of the AOP. The external review is conducted by experts not involved in the development of the specific AOP, who have scientific expertise in the hazard area/endpoint covered by the AOP.

There is an annual cycle of the AOP reviews; the internal reviews generally take place between February and April, while the external reviews are generally organised between September and December. The work plan contains more than 100 AOPs, most of them are currently under developemnt, while some are in a review cycle. With the increased number of AOPs being developed, individual AOPs will naturally form networks,
with some AOPs sharing Key Events (KE) and Adverse Outcomes (AO). Forming AOP networks of intersecting and interacting KEs and Key Event Relationships (KERs) may ultimately prove critical for the robustness of prediction of AOs.

AOP Knowledge Base

The AOP Knowledge Base (AOP KB) is a web-based platform which aims to bring together all knowledge on how chemicals can induce adverse effects, therefore providing a focal point for AOP development and dissemination. The project is jointly led by the OECD, the U.S. Environmental Protection Agency and the European Commission's Joint Research Center.

    • The first AOP KB module is the AOP Wiki: an interactive and virtual encyclopaedia for AOP development. It is structured in accordance with the original OECD "Guidance document and a template for developing and assessing adverse outcome pathways" (Series No. 184, Series on Testing and Assessment) and the more recent Handbook for AOP developers. The Wiki provides developers the necessary steps to capture the scientific information in a user-friendly manner.

    • Another AOP KB module is Effectopedia, especially adapated for the development of quantitative AOPs. Effectopedia is a knowledge aggregation and modeling platform designed for collaborative development and utilisation of AOPs. Originally built as a standalone project, Effectopedia is currently integrated as part of AOP KB. Effectopedia has a visually expressed modular structure providing summary information, containing a visual structure of the AOP, supporting the display of experimental data and offering the possibility to visualise response to response relationships between successive key events. This design places it at the forefront of AOP research, helping industry, governments and regulatory agencies to make toxicological predictions while simultaneously keeping the information open and accessible to the public. The first quantitative AOP examples are currently being developed in Effectopedia. It is expected that a downloadable version will be released at the end of 2016, followed by the development of an on-line version in 2017.


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